BACKGROUND: Asthma is a common respiratory disease caused by the interaction of genetic susceptibility and exposure to various environmental factors. Passive smoke exposure, characterized by parental smoking, has been shown to be a risk factor for the development of atopy and asthma. OBJECTIVE: We sought to perform a genome-wide linkage screen for asthma and bronchial hyperresponsiveness (BHR) and to determine the influence of passive tobacco smoke exposure during childhood on the results of genetic linkage studies to investigate gene-environment interactions. METHODS: A genome-wide linkage screen for asthma and BHR was performed in 200 families ascertained through a parent with asthma. Analyses were performed separately for the entire sample and for the smoking-exposed and nonexposed families. RESULTS: For asthma and BHR, the strongest evidence for linkage was observed for chromosomes 3p and 5q. The families in which the children were exposed to passive smoking accounted for the evidence for linkage of BHR to 5q ( P < .001), but evidence for linkage to 3p was found in both sets of families. Similar results were observed for asthma. However, there was no observed difference in the frequency of asthma or BHR in the offspring from the smoke-exposed compared with the nonexposed families. CONCLUSION: The results from this study demonstrate that the influence of susceptibility genes for a common disease such as asthma might not be apparent unless there is the appropriate exposure to environmental stimuli, such as passive exposure to cigarette smoke. This approach should be useful for identification of asthma susceptibility genes.
BACKGROUND:Asthma is a common respiratory disease caused by the interaction of genetic susceptibility and exposure to various environmental factors. Passive smoke exposure, characterized by parental smoking, has been shown to be a risk factor for the development of atopy and asthma. OBJECTIVE: We sought to perform a genome-wide linkage screen for asthma and bronchial hyperresponsiveness (BHR) and to determine the influence of passive tobacco smoke exposure during childhood on the results of genetic linkage studies to investigate gene-environment interactions. METHODS: A genome-wide linkage screen for asthma and BHR was performed in 200 families ascertained through a parent with asthma. Analyses were performed separately for the entire sample and for the smoking-exposed and nonexposed families. RESULTS: For asthma and BHR, the strongest evidence for linkage was observed for chromosomes 3p and 5q. The families in which the children were exposed to passive smoking accounted for the evidence for linkage of BHR to 5q ( P < .001), but evidence for linkage to 3p was found in both sets of families. Similar results were observed for asthma. However, there was no observed difference in the frequency of asthma or BHR in the offspring from the smoke-exposed compared with the nonexposed families. CONCLUSION: The results from this study demonstrate that the influence of susceptibility genes for a common disease such as asthma might not be apparent unless there is the appropriate exposure to environmental stimuli, such as passive exposure to cigarette smoke. This approach should be useful for identification of asthma susceptibility genes.
Authors: Manuel A R Ferreira; Louise O'Gorman; Peter Le Souëf; Paul R Burton; Brett G Toelle; Colin F Robertson; Peter M Visscher; Nicholas G Martin; David L Duffy Journal: Am J Hum Genet Date: 2005-10-14 Impact factor: 11.025
Authors: Gregory A Hawkins; Kelan Tantisira; Deborah A Meyers; Elizabeth J Ampleford; Wendy C Moore; Barbara Klanderman; Stephen B Liggett; Stephen P Peters; Scott T Weiss; Eugene R Bleecker Journal: Am J Respir Crit Care Med Date: 2006-08-24 Impact factor: 21.405
Authors: Emmanuelle Bouzigon; Paola Forabosco; Gerard H Koppelman; William O C M Cookson; Marie-Hélène Dizier; David L Duffy; David M Evans; Manuel A R Ferreira; Juha Kere; Tarja Laitinen; Giovanni Malerba; Deborah A Meyers; Miriam Moffatt; Nicholas G Martin; Mandy Y Ng; Pier Franco Pignatti; Mathias Wjst; Francine Kauffmann; Florence Demenais; Cathryn M Lewis Journal: Eur J Hum Genet Date: 2010-01-13 Impact factor: 4.246
Authors: Victor E Ortega; Gregory A Hawkins; Stephen P Peters; Eugene R Bleecker Journal: Immunol Allergy Clin North Am Date: 2007-11 Impact factor: 3.479